Further treatment with MPTP does not produce parkinsonism in marmosets showing behavioural recovery from motor deficits induced by an earlier exposure to the toxin

A. Ueki, P. N. Chong, A. Albanese, S. Rose, J. K. Chivers, P. Jenner, C. D. Marsden

Research output: Contribution to journalArticle

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or 0.9% saline, was administered to a group of common marmosets initially treated with the toxin 12-18 months previously. Initial treatment had consisted of a cumulative dose of 6-22 mg/kg (i.p.) which caused marked parkinsonism. Subsequently, the animals gradually recovered normal motor function. Further treatment consisted of a cumulative dose of MPTP of 78-83 mg/kg (i.p.) but this produced only modest akinesia. At 12-18 months after the initial treatment with MPTP, the content of dopamine, HVA and DOPAC in the caudate and putamen was markedly reduced. However, levels of dopamine, HVA and DOPAC in the nucleus accumbens were normal. Three months after the second treatment with MPTP there was no further decrease in the content ofdopamine in the caudate-putamen. However, in the nucleus accumbens the content of dopamine, HVA and DOPAC was now reduced. The initial treatment with MPTP substantially decreased the binding of [3H]mazindol in the caudateputamen but less so in the nucleus accumbens. Only a small additional decrease occurred upon further treatment with MPTP. The density of tyrosine hydroxylase (TH) immunoreactive cells in substantia nigra was reduced after the initial treatment with MPTP. However, the cell loss was far less marked than the decrease in terminal density, assessed by the binding of [3H]mazindol. Subsequent treatment with MPTP caused a small further loss of tyrosine hydroxylase-positive cells. Initial treatment with MPTP may kill the majority of MPTP-sensitive dopamine cells in the nigra. Compensation by the remaining nigrostriatal neurones may account for the behavioural recovery observed. Alternatively, initial treatment with MPTP may strip surviving neurones of their terminals so that uptake of the active metabolite MPP+ is reduced and its toxicity restricted.

Original languageEnglish
Pages (from-to)1089-1097
Number of pages9
JournalNeuropharmacology
Volume28
Issue number10
DOIs
Publication statusPublished - 1989

Keywords

  • common marmoset
  • MPTP
  • parkinsonism
  • recovery
  • tolerance

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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